Sleep deprivation is a global health problem adversely affecting health as well as causing decrements in learning and performance. Sleep deprivation induces significant changes in gene transcription in many brain regions, with the hippocampus particularly susceptible to acute sleep deprivation. However, less is known about the impacts of sleep deprivation on post-transcriptional gene regulation. To identify the effects of sleep deprivation on the translatome, we took advantage of the RiboTag mouse line to express HA-labeled Rpl22 in CaMKIIα neurons to selectively isolate and sequence mRNA transcripts associated with ribosomes in excitatory neurons. We found 198 differentially expressed genes in the ribosome-associated mRNA subset after sleep deprivation. In comparison with previously published data on gene expression in the hippocampus after sleep deprivation, we found that the subset of genes affected by sleep deprivation was considerably different in the translatome compared with the transcriptome, with only 49 genes regulated similarly. Interestingly, we found 478 genes differentially regulated by sleep deprivation in the transcriptome that were not significantly regulated in the translatome of excitatory neurons. Conversely, there were 149 genes differentially regulated by sleep deprivation in the translatome but not in the whole transcriptome. Pathway analysis revealed differences in the biological functions of genes exclusively regulated in the transcriptome or translatome, with protein deacetylase activity and small GTPase binding regulated in the transcriptome and unfolded protein binding, kinase inhibitor activity, neurotransmitter receptors and circadian rhythms regulated in the translatome. These results indicate that sleep deprivation induces significant changes affecting the pool of actively translated mRNAs.

中文翻译：

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TRAP-Seq 发现急性睡眠剥夺引起的转化变化

睡眠不足是一个全球性健康问题，会对健康产生不利影响，并导致学习和表现下降。睡眠剥夺会导致许多大脑区域的基因转录发生显着变化，其中海马体特别容易受到急性睡眠剥夺的影响。然而，人们对睡眠剥夺对转录后基因调控的影响知之甚少。为了确定睡眠剥夺对翻译组的影响，我们利用 RiboTag 小鼠系在 CaMKIIα 神经元中表达 HA 标记的 Rpl22，以选择性地分离和测序与兴奋性神经元中核糖体相关的 mRNA 转录本。我们在睡眠剥夺后核糖体相关 mRNA 子集中发现了 198 个差异表达基因。与之前发表的睡眠剥夺后海马基因表达数据相比，我们发现受睡眠剥夺影响的基因子集在翻译组中与转录组中存在显着差异，只有 49 个基因受到类似的调控。有趣的是，我们在转录组中发现了 478 个受睡眠剥夺差异调节的基因，而在兴奋性神经元的翻译组中没有显着调节。相反，翻译组中有 149 个基因受到睡眠剥夺的差异调节，但整个转录组中没有。通路分析揭示了仅在转录组或翻译组中调节的基因的生物学功能的差异，其中蛋白质脱乙酰酶活性和小GTP酶结合在转录组中受到调节，而未折叠蛋白结合、激酶抑制剂活性、神经递质受体和昼夜节律在翻译组中受到调节。这些结果表明，睡眠剥夺会引起显着变化，影响活跃翻译的 mRNA 池。